Elsevier

Thrombosis Research

Volume 77, Issue 6, 15 March 1995, Pages 515-530
Thrombosis Research

Influence of hormones on platelet intracellular calcium

https://doi.org/10.1016/0049-3848(95)00027-5Get rights and content

Abstract

The pathophysiology of thromboembolic disease associated with estrogen therapy is poorly understood. There are innumerable calciumdependent activities involved in platelet function. To determine whether platelet calcium levels are affected by exogenous hormones, intracellular calcium and release were studied in platelets in various hormonal environments and findings were correlated with platelet adhesion and aggregation. Platelet intracellular calcium concentration and release was significantly decreased in women ingesting tamoxifen compared to controls and significantly increased, as was platelet adhesion, in oral contraceptive users. Platelets incubated ex vivo with estradiol had increased intracellular calcium and release but there was decreased adhesion to fibronectin. Intracellular calcium concentration and release were not affected when platelets were incubated with tamoxifen. Adhesion to collagen III was increased in tamoxifen-incubated platelets. Only oral contraceptive users had increased sensitivity to aggregating agents. This data suggests that 17β estradiol, progesterone, and tamoxifen likely have a nongenomic effect on platelet intracellular calcium and calcium release and that platelet calcium levels are closely related to the degree of platelet adhesion and aggregation in vivo.

References (57)

  • LieberherrM.

    Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts

    J. Biol. Chem.

    (1987)
  • CivitelliR. et al.

    Nongenomic activation of the calcium message system by vitamin D metabolites in osteoblast-like cells

    Endocrinology

    (1990)
  • SutherlandR.L. et al.

    High-affinity anti-oestrogen binding site distinct from the oestrogen receptor

    Nature (Lond.)

    (1980)
  • LazierC.B.

    Interactions of tamoxifen in the chicken

    J. Steroid Biochem.

    (1987)
  • GreenbergD.A. et al.

    Calcium channel antagonist properties of the antineoplastic antiestrogen tamoxifen in the PC12 neurosecretory cell line

    Cancer Res.

    (1987)
  • McEverR.P.

    The clinical significance of platelet membrane glycoproteins

    Hematology/Oncology Clinics of North America

    (1990)
  • StadelB.V.

    Oral contraceptives and cardiovascular disease

    N. Engl. J. Med.

    (1981)
    StadelB.V.

    Oral contraceptives and cardiovascular disease

    N. Engl. J. Med.

    (1981)
  • HelmrichS.P. et al.

    Venous thromboembolism in relation to oral contraceptive use

    Obstet. Gynecol.

    (1987)
  • ByarD.P. et al.

    Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies

  • DeVoogtH.J. et al.

    Cardiovascular side effects of diethylstilbestrol, crypterone acetate, medroxyprogesterone acetate and extramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762

    J. Urol.

    (1986)
  • EnckR.E. et al.

    Tamoxifen treatment of metastatic breast cancer and antithrombin III levels

    Cancer

    (1984)
  • FisherB. et al.

    A randomized trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen receptor-positive tumors

    N. Engl. J. Med.

    (1989)
  • DoresG.M. et al.

    Platelet adhesion at low shear rate: study of a normal population

    Thromb. Res.

    (1993)
  • BornG.V.R. et al.

    The aggregation of blood platelets

    J. Physiol.

    (1963)
  • GrynkiewiczG. et al.

    A new generation of Ca2+ indicators with greatly improved fluorescence properties

    J. Biol. Chem.

    (1985)
  • BatchelorG.K.
  • KaneR.L.

    Spatio-temporal dynamics of human platelet adhesion in a HeleShaw flow chamber

  • Miller M.E., Dores G.M., Thorpe S.L. and Akerley W.L. Paradoxical influence of estrogenic hormones on...
  • Cited by (26)

    • Reference intervals for platelet aggregation assessed by multiple electrode platelet aggregometry

      2012, Thrombosis Research
      Citation Excerpt :

      Melamed et al. suggested that the gender differences might be caused by estrogen [19,21,23]. However, studies on this hypothesis are scarce and conflicting [24–28]. We found the day-to-day variation to be lower for ADPtest, ASPItest and COLtest compared to Seyfret et al. who used Na-citrated whole blood [4].

    • Mifepristone (RU 486) induces vasodilation and inhibits platelet aggregation: Nongenomic and genomic action to cause hemorrhage

      2011, Contraception
      Citation Excerpt :

      It is important to emphasize that this instantaneous effect was observed in the anucleate human platelets, which cannot be mediated by intracellular receptor occupancy, indicating that mifepristone is also acting at a nongenomic level to inhibit platelet aggregation. In this respect, earlier studies suggested that steroids possess direct nongenomic effects to alter platelet physiology [30,31]. Recently, it has been documented that progesterone and some of its metabolites cause platelet aggregation by increasing intracellular Ca2+ concentration [32].

    • Membrane lipid rafts coordinate estrogen-dependent signaling in human platelets

      2007, Biochimica et Biophysica Acta - Molecular Cell Research
    • Nongenomic effects of 17β-estradiol in human platelets: Potentiation of thrombin-induced aggregation through estrogen receptor β and Src kinase

      2005, Blood
      Citation Excerpt :

      Moreover, estrogen has been found to alter the metabolism of plasma lipoproteins, promoting a decrease in low-density lipoprotein levels and a concomitant increase in high-density lipoprotein levels.14 The role of sex steroid hormones in the regulation of platelet function has been investigated for years, but conflicting results have been reported.15-21 Many of the discrepancies can be ascribed to the different experimental models analyzed.

    View all citing articles on Scopus
    View full text